Some effects on blood coagulation of erythrocytes and other cells.

The activity of intact cells or of extracts from cells may be studied in blood coagulation systems to elucidate the problems of coagulation or to investigate the properties of cells and their extracts. The present report is concerned primarily with the latter objective. Since the beginning of this century aqueous extracts of cells have been known to accelerate clotting. In 1916 McLean prepared a protein-free accelerator from brain by extraction with lipid solvents. Crosbie and Scarborough (1941) reported that the clotting time of plasma when Russell viper venom was used was accelerated by the haemolysis of red cells. They suggested that this acceleration might be due to a highly active phospholipid. Quick, Georgatsos, and Hussey (1954) also reported the coagulant activity of red cell haemolysates, and Hussey and Kaser (1956) prepared an active phospholipid extract of red cell stroma and called it erythrocytin. If platelets are removed by centrifugation from citrated plasma, on recalcification this plasma clots badly; if platelets are added to such plasma, the clotting process reverts to normal. Using platelet-poor plasma as a substrate, substances of known chemical structure or tissue extracts or intact cells may be added in order to see what will correct the defect as completely as platelets themselves. Material which can substitute for platelets will be called " active " and that which has no effect will be called " inactive." A chemical substance or tissue extract which exhibits full activity is almost certain to contain cephalin-like molecules, and these must be either free or " available " at the surface of a larger molecule (O'Brien, 1958). It is still possible that there are chemical configurations other than the cephalins that could mimic the action of platelets, but the definition of "activity " remains and is a useful concept. This report is not immediately concerned with the thromboplastic substance found, for example, in a saline extract of brain, which has properties quite different from those of platelet-lipid, but such a brain extract contains active lipids (McLean, 1916) and these are " available " for tests able to detect platelet-like activity. In brain extracts the active lipid is combined with a protein and both components seem to play a part in determining its thromboplastic power (Mills, 1921; Chargaff, Ziff, and Cohen, 1940). In studying some tissue extracts advantage was taken of the species specificity (Trevan and Macfarlane, 1936) of the brain-like activity to exclude it. Many human tissue extracts possess this activity in varying degree when tested in human plasma. Guinea-pig tissue extracts, when tested in human plasma, exhibit platelet-like activity but no brainlike activity.